1. Field of the Invention
The invention relates to a powder inhaler with a mouthpiece for dispersing pharmaceutical medicament formulations, which has an auxiliary energy source in the form of a pressure medium system, and with a device for supplying a powder formulation, wherein on activation of the pressure medium system a gaseous pressure medium released by the pressure medium system forms an aerosol with the powder formulation such that the powder particles are present in dispersed form in the gaseous pressure medium.
Powder inhalers of this kind are needed for preparing inhalable medicaments. For diseases of the pulmonary and bronchial region, in particular, the medicaments are required and provided as inhalable pharmaceuticals (inhalants).
2. Description of the Prior Art
Within the scope of the present invention, the term “medicament” refers to the active ingredient of a pharmaceutical that is usually also known as a drug or active substance.
The term “medicament formulation” refers to powdered formulations that contain the medicament and are suitable for administration by inhalation in humans or animals. Usually, the active substance is mixed with adjuvants and additives.
In inhalers, the formulations are normally stored or kept in a reservoir and, for this reason, the formulations used must have sufficient stability on storage. Excipients may be added to the medicament for this purpose, to adjust the physico-chemical properties which affect the quality-determining parameters, such as availability and durability in a desirable manner.
The medicament formulation stored in the powder inhaler is nebulized and breathed in by the patient as an aerosol. The medicament is prepared in an inhalable form.
However, in this process, it is not usual for the entire measured dose to be expelled as an aerosol, but only part of it. This is due to the fact that some of the powder formulation is left behind in the storage container, merely subjected to turbulence, and then re-deposited elsewhere in the inhaler.
The proportion of the measured dose that leaves the mouthpiece of the powder inhaler is referred to as the delivered dose. Powder particles can only enter the lungs during the inhaling process if the aerodynamic particle diameter is less than 5 μm. The result of this is that only a proportion of the delivered dose can actually reach the lungs. This proportion can only be determined by laborious tests on the patient. For this reason, in vitro tests have been developed in which a simple laboratory experiment is used to determine the aerodynamic fine content, which corresponds to the lung-bound part of the delivered dose. The aerodynamic fine content is defined as the proportion of the measured dose in percent that has an aerodynamic particle diameter of less than 5.8 μm.
Within the scope of the present invention, the aerodynamic particle diameter is the particle diameter that corresponds to the equivalent diameter of a ball of density 1 g/cm3 that has the same sedimentation speed in air as the examined particle. To achieve the highest possible aerodynamic fine particle content, the following considerations are crucial.
First of all, a powder formulation must be prepared which contains the medicament in micronized form. The majority of all medicament particles should range from 1-5 μm in size. As micronized powders, being bulk materials, exhibit a high tendency to form particle agglomerates, the powder formulation usually contains excipients that make it easier to break up the micronized medicament particles and also increase their flow properties. Another parameter that is relevant to the quality of the powder formulation is its chemical and physical stability. Chemical stability is ensured if the medicament does not change into breakdown products on storage. Physical stability indicates that the aerodynamic fine content measured does not change during the storage period.
A suitable powder inhaler must convert a defined quantity of the powder formulation, i.e., the measured dose, into an aerosol during the inhaling process by the patient, while the highest possible values must be achieved for the delivered dose and the aerodynamic fine particle content. To achieve this, an important function of the powder inhaler is to break up the particle agglomerates of the medicament contained in the bulk powder formulation as efficiently as possible, as larger particles are deposited in the mouth and throat when breathed in and only particles with aerodynamic particle diameters of less than 5 μm reach the lungs. Thus, there is a more or less great difference between the proportion of the delivered dose based on the measured dose and the aerodynamic fine particle content, which is critically influenced by the efficiency of nebulization.
Against the background of the above remarks, the particle size must be reproducible within narrow limits so as to prevent fluctuations in the delivered dose and the aerodynamic fine content. On each actuation of the inhaler, roughly the same amount of medicament should be administered, while the delivered doses should have roughly the same size distributions of the particles of medicament.
However, from the point of view of efficiency and the most economical use of medicaments, it is also desirable to produce the largest possible aerodynamic fine particle content, as defined above.
In the prior art, there are basically two different systems of powder inhalers.
First, the so-called “passive” inhalers generally use the air breathed in by the patient to nebulize the powder formulation without any additional auxiliary energy sources—for example in the form of compressed air. These powder inhalers are designed so that powder is either contained in a prefabricated capsule in the form of a single dose (premetered dose), for example, or a number of premetered doses are held in readiness in a multi dose container inserted in the inhaler. During use, the capsule or one of the multi dose containers is pierced and the powder is emptied out and nebulized using the air breathed in by the patient.
The powder may also be present in the inhaler as a powder supply (bulk powder), an individual dose being prepared by means of a metering device before being transported out of the inhaler in the patient's air stream.
It is obvious that, with the powder inhalers described, the aerodynamic fine particle content is highly dependent on the patient's breathing maneuver.
Against the background of the above remarks it is now common to use so called “active” powder inhalers that use stored energy, e.g., pressurized gas. By using the pressurized gas for controlled expulsion and nebulization of the powder formulation, the process is made independent of the patient's breathing.
In order to achieve the break up of lumps and efficient nebulization and obtain the desired particle size and particle size distribution, essentially two methods have been used in the prior art.
In the case of some inhalers described in the literature, the breaking up of the powder is assisted by the impact of the particles on so called “impact surfaces.” Easing pressure, for example, the powder particles are deliberately directed against these impact surfaces to break up the particles. However, the result of this is that some of the powder particles striking the impact surface remain stuck to it and are deposited thereon. As a result, it is not possible to achieve a highly accurate and reproducible dosage as the powder particles deposited can accidentally be released again during subsequent inhalations.
One disadvantage is that, when pressurized gases are used to break up the lumps in powder formulations, very high aerosol speeds are reached. Very high aerosol speeds in turn mean that the proportion of the dose that reaches the lungs is reduced. Therefore, for powder inhalers operating with pressurized gases, additional spacers/separators are provided that have the task of reducing the speed of the aerosol particles formed.
These spacers/separators (or break up chambers), in which the speed of the powder particles is decelerated, are arranged in front of the mouthpiece of the inhaler and make the inhaler bulky and awkward to use. Inhalers for the pharmaceutical field should, however, be small and convenient so that the patient can carry the inhaler about with them at all times.